Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact

The nucleus of a cardiomyocyte has been increasingly recognized as a morphologically distinct and partially independent calcium (Ca(2+)) signaling microdomain, with its own Ca(2+)-regulatory mechanisms and important effects on cardiac gene expression. In this review, we (1) provide a comprehensive overview of the current state of research on the dynamics and regulation of nuclear Ca(2+) signaling in cardiomyocytes, (2) address the role of nuclear Ca(2+) in the development and progression of cardiac pathologies, such as heart failure and atrial fibrillation, and (3) discuss novel aspects of experimental methods to investigate nuclear Ca(2+) handling and its downstream effects in the heart. Finally, we highlight current challenges and limitations and recommend future directions for addressing key open questions.